A retrospective cohort study of the effect of rapid versus delayed-result procalcitonin testing on antibiotic use at a community hospital.

BACKGROUND: Procalcitonin is a serum biomarker used to distinguish bacterial infection from viral or noninfectious syndromes. Primary literature shows mixed data on use of procalcitonin for de-escalation of antimicrobials. Delays in test results of send-out procalcitonin assays may result in prolonged antimicrobial durations. It is unknown whether availability of rapid-result assays may shorten time to antibiotic de-escalation. AIM: This retrospective, cohort study compared antibiotic durations of treatment between groups with rapid-result versus delayed send-out, procalcitonin test modality. This study was exempt from Ethics Committee Approval, as determined by the Institutional Review Board at the study site. METHOD: Adult hospitalized patients were included if they had at least one procalcitonin test performed during the study period. The primary outcome compared mean duration of antimicrobial therapy between groups receiving a rapid-result procalcitonin test and a send-out test. Secondary outcomes included incidence of Clostridiodes difficile infection, mention of procalcitonin testing in the electronic medical record in reference to antimicrobial therapy decision making, and presence of comorbidities which affect procalcitonin levels independent of infection. RESULTS: A total of 350 lab results were analyzed. The duration of antimicrobial treatment between groups was not statistically different with the median duration of treatment in the send-out group being 2.95 days compared to 3.35 in the rapid result group, p = 0.856. Patient comorbidities with potential to lead to a noninfectious elevation or falsely high level of procalcitonin were common. CONCLUSION: Use of a rapid-result procalcitonin assay does not reduce hospital antimicrobial therapy duration as compared with send-out testing.

Modulation of dopamine release by ethanol is mediated by atypical GABAA receptors on cholinergic interneurons in the nucleus accumbens.

Previous studies indicate that moderate-to-high ethanol (EtOH) concentrations enhance dopamine (DA) neurotransmission in the mesolimbic DA system from the ventral tegmental area (VTA) and projecting to the nucleus accumbens core (NAc). However, voltammetry studies demonstrate that moderate-to-high EtOH concentrations decrease evoked DA release at NAc terminals. The involvement of γ-aminobutyric acid (GABA) receptors (GABAA Rs), glycine (GLY) receptors (GLYRs) and cholinergic interneurons (CINs) in mediating EtOH inhibition of evoked NAc DA release were examined. Fast scan cyclic voltammetry, electrophysiology, optogenetics and immunohistochemistry techniques were used to evaluate the effects of acute and chronic EtOH exposure on DA release and CIN activity in C57/BL6, CD-1, transgenic mice and δ-subunit knockout (KO) mice (δ-/-). Ethanol decreased DA release in mice with an IC50 of 80 mM ex vivo and 2.0 g/kg in vivo. GABA and GLY decreased evoked DA release at 1-10 mM. Typical GABAA R agonists inhibited DA release at high concentrations. Typical GABAA R antagonists had minimal effects on EtOH inhibition of evoked DA release. However, EtOH inhibition of DA release was blocked by the α4 ß3 δ GABAA R antagonist Ro15-4513, the GLYR antagonist strychnine and by the GABA ρ1 (Rho-1) antagonist TPMPA (10 µM) and reduced significantly in GABAA R δ-/- mice. Rho-1 expression was observed in CINs. Ethanol inhibited GABAergic synaptic input to CINs from the VTA and enhanced firing rate, both of which were blocked by TPMPA. Results herein suggest that EtOH inhibition of DA release in the NAc is modulated by GLYRs and atypical GABAA Rs on CINs containing δ- and Rho-subunits.

Interventions to increase uptake of Human Papillomavirus (HPV) vaccination in minority populations: A systematic review.

Minority youth represent a unique population for public health interventions given the social, economic, and cultural barriers they often face in accessing health services. Interventions to increase uptake of Human Papillomavirus (HPV) vaccination in minority youth have the potential to reduce disparities in HPV infection and HPV-related cancers. This systematic review assesses the effectiveness of interventions to increase HPV vaccine uptake, measured as vaccine series initiation and series completion, among adolescents and young adults, aged 9-26 years old, identifying as a racial and ethnic minority or sexual and gender minority (SGM) group in high-income countries. Of the 3013 citations produced by a systematic search of three electronic databases (PubMed, Embase, and Web of Science) in November 2018, nine studies involving 9749 participants were selected for inclusion. All studies were conducted in the United States and were published from 2015 to 2018. Interventions utilized education, vaccine appointment reminders, and negotiated interviewing to increase vaccination. Participants were Black or African American (44.4%), Asian (33.3%), Hispanic or Latinx (22.2%), American Indian or Alaska Native (11.1%), and SGM (22.2%). Studies enrolled parent-child dyads (33.3%), parents alone (11.1%), and youth alone (55.6%). Vaccine series initiation ranged from 11.1% to 84% and series completion ranged from 5.6% to 74.2% post-intervention. Educational and appointment reminder interventions may improve HPV vaccine series initiation and completion in minority youth in the U.S. Given the lack of high quality, adequately powered studies, further research is warranted to identify effective strategies for improving HPV vaccine uptake for minority populations.

A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2- Metastatic Breast Cancer.

PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA-mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2- advanced (locally unresectable) or metastatic disease (HR+/HER2- mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2- mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2- mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2- mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status.

A Systematic Literature Review of the Prognostic and Predictive Value of PIK3CA Mutations in HR+/HER2- Metastatic Breast Cancer.

PIK3CA mutations may have prognostic value for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer, representing an important potential target for systemic therapy. Prognostic and predictive values associated with PIK3CA mutations are not well understood. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and conference abstracts was performed for English-language articles published January 1993 through April 2019. Articles were categorized by treatment arms based on experimental and treatment drug classes. Information on progression-free survival (PFS), hazard ratios, overall survival, response rate, and clinical benefit rate was obtained. A total of 17 studies were included. Among those evaluating non-PI3Ki based therapies, 91% showed numerically shorter median PFS, ranging from 1.5 to 19.2 months and 1.8 to 29.6 months for the mutant versus non-mutant subgroups, respectively. Where reported (n = 13 studies), PFS was shorter between those arms offering endocrine monotherapy (range, 1.6-14.7 months) compared with a corresponding targeted therapy + endocrine monotherapy (range, 3.9-29.6 months). Of 5 PI3Ki-based arms comparing PFS, higher median PFS in PIK3CA mutant versus non-mutant cases was demonstrated. PFS was shorter for patients with PIK3CA mutant (range, 1.6-19.2 months) compared with PIK3CA wild-type (range, 1.8-29.6 months) in 10 (71%) of 14 treatment arms reporting PFS. Studies (n = 4) not reporting PFS reported response rate, but there were no clear directional trends. The presence of PIK3CA mutations may be associated with worse clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Clinical outcomes such as PFS may be improved using a combination of PI3Ki-based therapies and endocrine therapies among this population. However, more research is warranted to fully elucidate this association.